PD-L1 ⁺ neutrophils contribute to injury-induced infection susceptibility

Abstract

The underlying mechanisms contributing to injury-induced infection susceptibility remain poorly understood. Here, we describe a rapid increase in neutrophil cell numbers in the lungs following induction of thermal injury. These neutrophils expressed elevated levels of programmed death ligand 1 (PD-L1) and exhibited altered gene expression profiles indicative of a reparative population. Upon injury, neutrophils migrate from the bone marrow to the skin but transiently arrest in the lung vasculature. Arrested neutrophils interact with programmed cell death protein 1 (PD-1) on lung endothelial cells. A period of susceptibility to infection is linked to PD-L1+ neutrophil accumulation in the lung. Systemic treatment of injured animals with an anti–PD-L1 antibody prevented neutrophil accumulation in the lung and reduced susceptibility to infection but augmented skin healing, resulting in increased epidermal growth. This work provides evidence that injury promotes changes to neutrophils that are important for wound healing but contribute to infection susceptibility.

Specific NLRP3 Inflammasome Assembling and Regulation in Neutrophils: Relevance in Inflammatory and Infectious Diseases

“…Furthermore, as compared with classical neutrophils and PMN-MSDCs, N2 TAN produce higher levels of chemokines but lower granules and ROS [ 75 , 76 ]. PD-L1-expressing neutrophils have been identified in cancer, infections, autoimmunity, and sepsis [ 77 , 78 , 79 , 80 , 81 ] and appear to be less prone to apoptosis than their PDL-1-negative counterparts [ 81 ]. Interestingly, these PDL-1-expressing neutrophils suppress the immune response by limiting activity of PD-1-expressing cells [ 77 , 78 , 79 , 80 , 81 ], culminating in either a protective or deleterious role according to the pathological context.…”

PD-L1 maintains neutrophil extracellular traps release by inhibiting neutrophil autophagy in endotoxin-induced lung injury

“…Thanabalasuriar et al. ( 63 ) reported the role of PD-L1 + neutrophils in mice with airway inflammation and found a protective effect of anti-PD-L1 antibody against inflammation. Our previous work presented that upregulation of neutrophil PD-L1 in inflammatory states can delay the apoptotic process through the PI3K/Akt pathway and consequently induce lung injury ( 35 ).…”

“…However, Thanabalasuriar et al. reported that blocking PD-L1 reduces airway inflammation and systemic treatment of injured animals with an anti-PD-L1 antibody prevented neutrophil accumulation in the lung and reduced susceptibility to infection ( 63 ). We verified the protective effect of anti-PD-L1 antibody against lung injury, the reduction of NET release and enhanced autophagy in vivo using a mice ARDS model.…”

Early detection of soluble CD27, BTLA, and TIM-3 predicts the development of nosocomial infection in pediatric burn patients

“…Both receptors have been well-validated, in human sepsis studies, to be upregulated on various immune cells, which leads to a dysregulated T cell response and subsequent immunosuppression ( 69 , 70 ). Similarly, burn murine models have exhibited increased PD-1, but this research is still relatively limited in terms of human thermal injuries and is non-existent in pediatrics ( 65 , 71 , 72 ). Within the present study, percent PD-1 expression on CD4+ lymphocytes was elevated for burn patients within the first 3 days of injury relative to HC ( Figure 2G ).…”